Extended Data Fig. 9: Identifying aging and AD pathogenesis-associated gene expression signatures. | Nature Genetics

Extended Data Fig. 9: Identifying aging and AD pathogenesis-associated gene expression signatures.

From: A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains

Extended Data Fig. 9

a-f. Volcano plots showing the differentially expressed (DE) genes between adult (6 months) and aged (21 months) mice (a-b), between WT and EOAD (c-d) and between WT and LOAD (e-f). Significantly changed genes are colored by the main cell type identity. Examples with concordant changes across subclusters are labeled with related biological pathways. g. Scatter plot shows the correlation of the log2-transformed fold changes of 559 DE genes significantly changed within the same subcluster in both AD models compared to WT. h. Box plot displays the predicted age of 3-month-old WT mice (n = 4745 pseudobulk cells) against AD models (EOAD: n = 11959; LOAD: n = 25152) across various cell types, normalized by the mean predicted age of the WT samples. Stars indicate p-value < 0.05 (WT vs EOAD: p = 7.6 × 10-142; WT vs LOAD: p = 0) using the two-sided Wilcoxon rank-sum test. i. Box plots displaying the predicted biological age of 3-month-old wild-type mice against AD models, showing cell types and conditions demonstrating significant differences (FDR adjusted p-value < 0.05, two-sided Wilcoxon rank-sum test,). Values are normalized by the mean predicted age of the WT samples. Number of pseudobulk cells per box plot (left to right): 179, 615, 1190, 37, 85, 179, 1819, 3272, 7875, 87, 220, 498, 493, 1701, 3057, 85, 359, 673, 62, 338, 65, 194, 424, 11, 30, 56, 605, 1096, 2732, 427, 1389, 2403, 77, 261, 483, 49, 158, 298, 63, 276, 50, 302, 59, 216, 432, 293, 880, 1837, 19, 3, 8, 35, 226, 118, 1178. j. Box plots showing Zfp423 expression in dentate gyrus neurons (3 months = 301, 6 months = 204, 21 months = 334, EOAD = 192 and LOAD = 338 pseudobulk cells) and Neat1 expression in astrocytes (3 months = 968, 6 months = 969, 21 months = 700, EOAD = 615 and LOAD = 1190 pseudobulk cells) across various conditions. Both genes, ranking among the top predictors of age in their respective cell types, exhibited increased expression in the 3-month-old AD models (Zfp423 solely in the LOAD model, Neat1 in both AD models). For all box plots, boxes indicate the median and interquartile range (IQR) with whiskers indicating 1.5X IQR.

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